British Journal of Anaesthesia, xxx (xxx): xxx (xxxx)
CORRESPONDENCE
High-flow nasal-oxygenation-assisted fibreoptic tracheal
intubation in critically ill patients with COVID-19 pneumonia: a
prospective randomised controlled trial
Cai-Neng Wu1, Lin-Zhi Xia2, Kun-Hong Li2, Wu-Hua Ma1, Dong-Nan Yu1, Bo Qu1,
Bi-Xi Li2,* and Ying Cao1,*
1
Guangzhou, China and 2Wuhan, China
*Corresponding authors. E-mails: bxlee@sohu.com, yingcao1986@163.com
Keywords: airway management; COVID-19 pneumonia; high-flow nasal oxygenation; preoxygenation; tracheal
intubation
EditordSince December 2019, cases of pneumonia caused by
the coronavirus disease 2019 (COVID-19) have been reported
in Wuhan, Hubei Province, China. Coronavirus disease 2019
has spread rapidly around the globe, including Asia, North
America, Europe, and Africa.1 The 2019 novel coronavirus is
likely similar to Middle East respiratory syndrome
coronavirus and severe acute respiratory syndrome
coronavirus. They belong to the Betacoronavirus genus and
can cause severe respiratory disease, including acute
respiratory distress syndrome, pulmonary oedema, and
respiratory failure.2 Tracheal intubation for invasive
mechanical ventilation is the mainstay therapy to correct
hypoxaemia. Preoxygenation with the standard bag-valve
mask oxygenation followed by rapid-sequence intubation
has been proposed in non-severely hypoxaemic critically ill
patients requiring tracheal intubation to reduce the risk of
aspiration and desaturation. However, a previous study
reported that 23% of patients had SpO2 <90% during
intubation.3
Thus far, more than 80000 cases of COVID-19 have been
confirmed in China. Person-to-person transmission of COVID-
19 has been described, including in many healthcare
workers.4,5 Rapid-sequence fibreoptic bronchoscopic tracheal
intubation in patients with COVID-19 pneumonia may reduce
the risk of viral spread. We evaluated the efficacy and safety of
high-flow nasal oxygenation (HFNO) during fibreoptic bron-
choscopic intubation in critically ill patients with COVID-19
pneumonia compared with standard mask oxygenation
(SMO).
© 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
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This study was approved by the ethics committee of the
General Hospital of Central Theatre Command and registered
at http://www.chictr.org/cn/ (registration number:
ChiCTR2000029658). Inclusion criteria were adults (aged >18
yr), with clinically-confirmed COVID-19 pneumonia and
hypoxaemia (defined as the ratio of arterial oxygen tension
[PaO2] to inspiratory oxygen fraction [FIO2] <300 mm Hg), and
requiring intubation in the ICU. Patients were randomly allo-
cated to the HFNO group or the SMO group.
Patients were placed in the head-up supine position and
oxygen was administered for 4 min, either via high-flow nasal
cannula (AIRVO™ 2; Fisher & Paykel Healthcare, Auckland,
New Zealand) at 50 L min
1 with heated and humidified oxy-
gen at 37 C, or by standard bag-valve mask at 15 L min
1. All
patients were then instructed to take deep breaths before
general anaesthesia was induced with propofol 1.5e2.5 mg
kg
1 and neuromuscular block was initiated with rocuronium
1 mg kg
1. One minute after administration of rocuronium,
fibreoptic tracheal intubation was attempted by one of six
anaesthesiologists experienced in fibreoptic intubation. Each
anaesthesiologist intubated sequences of 10 patients who
were evenly divided into the two groups.
A 4.5 mm fibreoptic bronchoscope (UE Medical Company
Ltd, Zhejiang, China) loaded with a lubricated reinforced
Parker Flex-Tip® tracheal tube (Well Lead Medical Company
Ltd., Guangzhou, China) was inserted until the carina was
visualised, and the tube was advanced over the bronchoscope
into the trachea. During attempts at tracheal intubation, HFNO
was maintained for the HFNO group, whereas no oxygen was
e1
 e2 - Correspondence

administered for the SMO group. After removal of the bron-
choscope, successful intubation was confirmed by capnog-
raphy. If SpO2 <90% occurred during intubation, bronchoscopy
was terminated and face-mask ventilation was initiated to
correct desaturation. The primary endpoint was the total time
of intubation, defined as the sum of the time spent from the
beginning of bronchoscopy until proper tracheal tube place-
ment was confirmed. The secondary endpoints included the
lowest SpO2 during intubation, incidence of mask ventilation
for SpO2 <90%, PaO2/FIO2 before intubation, incidence of SpO2
<80% during intubation, incidence of minimum SpO2 >95%
during intubation, and 7 day mortality.
Sample size was calculated using PASS (version 10.0, NCSS
Statistical Software; NCSS LLC, Kaysville, UT, USA) based on
total time of intubation. We estimated that 27 patients per
group would be needed. Assuming the potential patient
dropout, 30 patients were required in each group for a total
sample size of 60 patients. Of 79 participants screened for
eligibility, 19 participants met the exclusion criteria and 60
patients were recruited for the study. One patient was
excluded for improving before the start of bronchoscopic
intubation, and one patient withdrew consent in the HFNO
group (Supplementary Fig. S1). Baseline characteristics were
similar between groups (Table 1). Intubation time was signif-
icantly shorter in the HFNO (69 [inter-quartile range {IQR}:
62.2e74.0] s) than in the SMO group (76 [68.0e90.5] s; P¼0.005).
Compared with the SMO group, the HFNO group had a greater
minimum SpO2 during tracheal intubation (94% [IQR:
92.1e95.8] vs 91% [86.3e93.0]; P¼0.001) and a lower incidence
of rescue face-mask ventilation (4% vs 27%; P¼0.015). There
was no significant difference in the proportion of patients with
minimum SpO2 >95% during intubation, in the incidence of
SpO2 <80% during intubation, or in the incidence of 7 day
mortality.
High-flow nasal oxygenation is effective in preventing
hypoxaemia, but there has been no study of its efficacy
during attempts at fibreoptic intubation in the ICU. High-
flow nasal oxygenation generates positive airway pressure
and can increase end-expiratory lung volume, thereby
improving oxygenation.6,7 Our results show that the lowest
SpO2 was higher in the HFNO group than the SMO group, and
that HFNO shortened the duration of intubation. The rea-
sons for this are not clear, but one possibility is that inter-
ruption of attempts at tracheal intubation to carry out rescue
face-mask ventilation was less frequently required in the
HFNO group.
A recent study of 138 patients showed that healthcare
workers comprised 29% of those infected, and suggested rapid
human-to-human transmission of COVID-19.5 As of February
11, 2020, 1716 medical workers were considered laboratory-
confirmed COVID-19 infections in China, with six fatal cases.
Direct laryngoscopy, inadequate sedation, coughing during
laryngoscopy, and manual ventilation are consistently asso-
ciated with increased risk of transmission as a result of the
generation of natural aerosols.8 Therefore, tracheal intubation
and mask ventilation are considered high-risk procedures as
they intensify viral spread.9,10 To reduce tracheal-intubation-
induced coughing and subsequent spread of virus, we rec-
ommended intubation after rapid-sequence intubation of
general anaesthesia using visual fibreoptic bronchoscopy.
Although we have no evidence that fibreoptic tracheal intu-
bation can prevent airborne viral transmission from patient to
healthcare provider, it may increase the distance between the
anaesthesiologist and the patient’s airway. The six anaes-
thesiologists in the current study are currently not infected.
According to the results of a recent study, HFNO use in pa-
tients with bacterial pneumonia was not associated with an
increase in air or surface contamination.11 In contrast, mask
ventilation before tracheal intubation can generate more
aerosols.
In conclusion, in critically ill patients with COVID-19
pneumonia, HFNO provided a shorter intubation time and
less frequent incidence of desaturation during attempts at
fibreoptic tracheal intubation compared with preoxygena-
tion by face-mask ventilation. High-flow nasal oxygenation
is potentially useful during rapid-sequence induction and
intubation in critically ill patients with COVID-19
pneumonia.

Table 1 General characteristics and outcomes of patients. Data shown as mean (standard deviation), median [inter-quartile range], or
n (%). Continuous data were compared using independent-sample t-test or ManneWhitney U-test. Proportions were analysed using
Fisher’s exact test or c2 test. HFNO, high-flow nasal oxygenation; SMO, standard mask oxygenation.

Characteristic Group HFNO Group SMO P-value

Patients, n 28 30
Sex, M/F 14/14 19/11
Age (yr) 64.3 (11.6) 67.1 (9.9)
Weight (kg) 66.9 (9.4) 70.3 (9.1)
Height (cm) 165.5 (8.7) 167.0 (7.8)
Ventilatory frequency 26.8 (5.9) 27.7 (5.3)
Co-morbidities, n (%)
Hypertension 16 (57.1) 19 (63.3)
Diabetes mellitus 3 (10.7) 2 (6.7)
Cardiovascular disease 8 (28.6) 10 (33.3)
Primary and secondary outcomes
PaO2/FIO2 before intubation 139.5 [118.3; 162.3] 128.5 [121.5; 136.3] 0.225
Total time to intubation (s) 68.5 [62.2; 74.0] 76.0 [68.0; 90.5] 0.005
Lowest SpO2 during intubation 94.0 [92.1; 95.8] 91.2 [86.3; 93.0] 0.001
Mask ventilation for SpO2 <90%, n (%) 1 (3.6) 8 (26.7) 0.015
Percentage of minimum SpO2 >95% during intubation, n (%) 8 (28.6) 3 (10) 0.071
Percentage of SpO2 <80% during intubation, n (%) 0 (0) 2 (6.7) 0.164

Authors’ contributions
Study design: B-XL, C-NW, YC
Study conduct: C-NW, B-XL, L-ZX, BQ
Data collection: B-XL, C-NW, W-HM, K-HL
Data analysis: YC, D-NY
Writing manuscript: C-NW, YC
All authors read and approved the final version of the
manuscript.
Declarations of interest
The authors declare that they have no conflicts of interest.
Funding
First Affiliated Hospital of Guangzhou University of Chinese
Medicine Innovation Foundation (2019QNO4).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.bja.2020.02.020.
10.
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